ID BGLR_HUMAN Reviewed; 651 AA. AC P08236; B4E1F6; E9PCV0; Q549U0; Q96CL9; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 231. DE RecName: Full=Beta-glucuronidase; DE EC=3.2.1.31 {ECO:0000305|PubMed:3355537}; DE AltName: Full=Beta-G1; DE Flags: Precursor; GN Name=GUSB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-649, AND ALTERNATIVE RP SPLICING. RC TISSUE=Placenta; RX PubMed=3468507; DOI=10.1073/pnas.84.3.685; RA Oshima A., Kyle J.W., Miller R.D., Hoffmann J.W., Powell P.P., Grubb J.H., RA Sly W.S., Tropak M., Guise K.S., Gravel R.A.; RT "Cloning, sequencing, and expression of cDNA for human beta- RT glucuronidase."; RL Proc. Natl. Acad. Sci. U.S.A. 84:685-689(1987). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT PRO-649. RC TISSUE=Lung; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-70. RX PubMed=1916806; DOI=10.1016/0888-7543(91)90192-h; RA Shipley J.M., Miller R.D., Wu B.M., Grubb J.H., Christensen S.G., RA Kyle J.W., Sly W.S.; RT "Analysis of the 5' flanking region of the human beta-glucuronidase gene."; RL Genomics 10:1009-1018(1991). RN [9] RP PROTEIN SEQUENCE OF 23-32 AND 160-175. RC TISSUE=Placenta; RX PubMed=1311180; DOI=10.1515/bchm3.1992.373.1.57; RA Tanaka J., Gasa S., Sakurada K., Miyazaki T., Kasai M., Makita A.; RT "Characterization of the subunits and sugar moiety of human placental and RT leukemic beta-glucuronidase."; RL Biol. Chem. Hoppe-Seyler 373:57-62(1992). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 520-585. RC TISSUE=Fibroblast; RX PubMed=3924735; DOI=10.1016/0378-1119(85)90300-2; RA Guise K.S., Korneluk R.G., Waye J., Lamhonwah A.-M., Quan F., Palmer R., RA Ganschow R.E., Sly W.S., Gravel R.A.; RT "Isolation and expression in Escherichia coli of a cDNA clone encoding RT human beta-glucuronidase."; RL Gene 34:105-110(1985). RN [11] RP INHIBITION BY L-ASPARTIC ACID. RX PubMed=11568288; DOI=10.1203/00006450-200110000-00007; RA Kreamer B.L., Siegel F.L., Gourley G.R.; RT "A novel inhibitor of beta-glucuronidase: L-aspartic acid."; RL Pediatr. Res. 50:460-466(2001). RN [12] RP CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=3355537; DOI=10.1042/bj2500547; RA Powell P.P., Kyle J.W., Miller R.D., Pantano J., Grubb J.H., Sly W.S.; RT "Rat liver beta-glucuronidase. cDNA cloning, sequence comparisons and RT expression of a chimeric protein in COS cells."; RL Biochem. J. 250:547-555(1988). RN [13] RP GLYCOSYLATION AT ASN-272. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-272. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-173; ASN-272 AND ASN-631. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS). RX PubMed=8599764; DOI=10.1038/nsb0496-375; RA Jain S., Drendel W.B., Chen Z.W., Mathews F.S., Sly W.S., Grubb J.H.; RT "Structure of human beta-glucuronidase reveals candidate lysosomal RT targeting and active-site motifs."; RL Nat. Struct. Biol. 3:375-381(1996). RN [19] RP REVIEW ON VARIANTS. RX PubMed=19224584; DOI=10.1002/humu.20828; RA Tomatsu S., Montano A.M., Dung V.C., Grubb J.H., Sly W.S.; RT "Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly RT Syndrome)."; RL Hum. Mutat. 30:511-519(2009). RN [20] RP VARIANT MPS7 TRP-216. RX PubMed=8111412; DOI=10.1002/humu.1380020604; RA Vervoort R., Lissens W., Liebaers I.; RT "Molecular analysis of a patient with hydrops fetalis caused by beta- RT glucuronidase deficiency, and evidence for additional pseudogenes."; RL Hum. Mutat. 2:443-445(1993). RN [21] RP VARIANTS MPS7 VAL-354 AND TRP-611. RX PubMed=8111413; DOI=10.1002/humu.1380020605; RA Wu B.M., Sly W.S.; RT "Mutational studies in a patient with the hydrops fetalis form of RT mucopolysaccharidosis type VII."; RL Hum. Mutat. 2:446-457(1993). RN [22] RP VARIANTS MPS7 CYS-382 AND VAL-619. RX PubMed=1702266; RA Tomatsu S., Fukuda S., Sukegawa K., Ikedo Y., Yamada S., Yamada Y., RA Sasaki T., Okamoto H., Kuwahara T., Yamaguchi S., Kiman T., Shintaku H., RA Isshiki G., Orii T.; RT "Mucopolysaccharidosis type VII: characterization of mutations and RT molecular heterogeneity."; RL Am. J. Hum. Genet. 48:89-96(1991). RN [23] RP VARIANT MPS7 CYS-627. RX PubMed=7680524; RA Shipley J.M., Klinkenberg M., Wu B.M., Bachinsky D.R., Grubb J.H., RA Sly W.S.; RT "Mutational analysis of a patient with mucopolysaccharidosis type VII, and RT identification of pseudogenes."; RL Am. J. Hum. Genet. 52:517-526(1993). RN [24] RP VARIANT MPS7 PHE-176, AND VARIANT PRO-649. RX PubMed=8089138; DOI=10.1016/s0021-9258(17)31569-7; RA Wu B.M., Tomatsu S., Fukuda S., Sukegawa K., Orii T., Sly W.S.; RT "Overexpression rescues the mutant phenotype of L176F mutation causing RT beta-glucuronidase deficiency mucopolysaccharidosis in two Mennonite RT siblings."; RL J. Biol. Chem. 269:23681-23688(1994). RN [25] RP VARIANT MPS7 PHE-176, VARIANT ASN-152, AND CHARACTERIZATION OF VARIANT RP ASN-152. RX PubMed=7573038; RA Vervoort R., Islam M.R., Sly W., Chabas A., Wevers R., de Jong J., RA Liebaers I., Lissens W.; RT "A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene."; RL Am. J. Hum. Genet. 57:798-804(1995). RN [26] RP VARIANTS MPS7 SER-148 AND CYS-495. RX PubMed=7633414; DOI=10.1093/hmg/4.4.651; RA Yamada S., Tomatsu S., Sly W.S., Islam R., Wenger D.A., Fukuda S., RA Sukegawa K., Orii T.; RT "Four novel mutations in mucopolysaccharidosis type VII including a unique RT base substitution in exon 10 of the beta-glucuronidase gene that creates a RT novel 5'-splice site."; RL Hum. Mol. Genet. 4:651-655(1995). RN [27] RP VARIANTS MPS7 ARG-136; LYS-150; PHE-176; TRP-216; CYS-320; SER-320; RP TYR-351; CYS-374; CYS-382; HIS-382; PRO-435; TRP-477; CYS-508; ASP-572; RP ASN-606 AND CYS-627. RX PubMed=8644704; RA Vervoort R., Islam M.R., Sly W.S., Zabot M.T., Kleijer W.J., Chabas A., RA Fensom A., Young E.P., Liebaers I., Lissens W.; RT "Molecular analysis of patients with beta-glucuronidase deficiency RT presenting as hydrops fetalis or as early mucopolysaccharidosis VII."; RL Am. J. Hum. Genet. 58:457-471(1996). RN [28] RP VARIANTS MPS7 SER-408 AND LEU-415. RX PubMed=8707294; DOI=10.1007/s004390050207; RA Islam M.R., Vervoort R., Lissens W., Hoo J.J., Valentino L.A., Sly W.S.; RT "beta-Glucuronidase P408S, P415L mutations: evidence that both mutations RT combine to produce an MPS VII allele in certain Mexican patients."; RL Hum. Genet. 98:281-284(1996). RN [29] RP VARIANT MPS7 PHE-52, AND CHARACTERIZATION OF VARIANT MPS7 PHE-52. RX PubMed=9099834; DOI=10.1007/s004390050389; RA Vervoort R., Buist N.R., Kleijer W.J., Wevers R., Fryns J.P., Liebaers I., RA Lissens W.; RT "Molecular analysis of the beta-glucuronidase gene: novel mutations in RT mucopolysaccharidosis type VII and heterogeneity of the polyadenylation RT region."; RL Hum. Genet. 99:462-468(1997). RN [30] RP VARIANT ASN-152, AND VARIANTS MPS7 GLY-38 AND HIS-626. RX PubMed=9490302; DOI=10.1007/s004390050656; RA Vervoort R., Gitzelmann R., Bosshard N., Maire I., Liebaers I., Lissens W.; RT "Low beta-glucuronidase enzyme activity and mutations in the human beta- RT glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency RT and a heterozygote."; RL Hum. Genet. 102:69-78(1998). RN [31] RP VARIANT MPS7 PHE-176. RX PubMed=12859417; DOI=10.1034/j.1399-0004.2003.00119.x; RA Schwartz I., Silva L.R., Leistner S., Todeschini L.A., Burin M.G., RA Pina-Neto J.M., Islam R.M., Shah G.N., Sly W.S., Giugliani R.; RT "Mucopolysaccharidosis VII: clinical, biochemical and molecular RT investigation of a Brazilian family."; RL Clin. Genet. 64:172-175(2003). RN [32] RP VARIANTS MPS7 ASN-350 AND LEU-577, AND CHARACTERIZATION OF VARIANT MPS7 RP ASN-350 LEU-577. RX PubMed=12522561; DOI=10.1007/s00439-002-0849-5; RA Storch S., Wittenstein B., Islam R., Ullrich K., Sly W.S., Braulke T.; RT "Mutational analysis in longest known survivor of mucopolysaccharidosis RT type VII."; RL Hum. Genet. 112:190-194(2003). CC -!- FUNCTION: Plays an important role in the degradation of dermatan and CC keratan sulfates. CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-glucuronoside + H2O = an alcohol + D-glucuronate; CC Xref=Rhea:RHEA:17633, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, CC ChEBI:CHEBI:58720, ChEBI:CHEBI:83411; EC=3.2.1.31; CC Evidence={ECO:0000305|PubMed:3355537}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17634; CC Evidence={ECO:0000305|PubMed:3355537}; CC -!- ACTIVITY REGULATION: Inhibited by L-aspartic acid. CC -!- SUBUNIT: Homotetramer. CC -!- SUBCELLULAR LOCATION: Lysosome. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Long; CC IsoId=P08236-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P08236-2; Sequence=VSP_001799; CC Name=3; CC IsoId=P08236-3; Sequence=VSP_054830; CC -!- PTM: N-linked glycosylated with 3 to 4 oligosaccharide chains. CC {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:16335952, CC ECO:0000269|PubMed:19159218}. CC -!- DISEASE: Mucopolysaccharidosis 7 (MPS7) [MIM:253220]: A form of CC mucopolysaccharidosis, a group of lysosomal storage diseases CC characterized by defective degradation of glycosaminoglycans, resulting CC in their excessive accumulation and secretion. The diseases are CC progressive and often display a wide spectrum of clinical severity. CC MPS7 is an autosomal recessive form with a highly variable phenotype, CC ranging from severe lethal hydrops fetalis to mild forms with survival CC into adulthood. Most patients with the intermediate phenotype show CC hepatomegaly, skeletal anomalies, coarse facies, and variable degrees CC of mental impairment. {ECO:0000269|PubMed:12522561, CC ECO:0000269|PubMed:12859417, ECO:0000269|PubMed:1702266, CC ECO:0000269|PubMed:7573038, ECO:0000269|PubMed:7633414, CC ECO:0000269|PubMed:7680524, ECO:0000269|PubMed:8089138, CC ECO:0000269|PubMed:8111412, ECO:0000269|PubMed:8111413, CC ECO:0000269|PubMed:8644704, ECO:0000269|PubMed:8707294, CC ECO:0000269|PubMed:9099834, ECO:0000269|PubMed:9490302}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M15182; AAA52561.1; -; mRNA. DR EMBL; AK303819; BAG64768.1; -; mRNA. DR EMBL; AK223406; BAD97126.1; -; mRNA. DR EMBL; AC073261; AAQ96851.1; -; Genomic_DNA. DR EMBL; CH236961; EAL23740.1; -; Genomic_DNA. DR EMBL; CH471140; EAX07951.1; -; Genomic_DNA. DR EMBL; BC014142; AAH14142.1; -; mRNA. DR EMBL; M65002; AAA52622.1; -; Genomic_DNA. DR EMBL; M10618; AAA52621.1; -; mRNA. DR EMBL; S72462; AAD14101.1; -; Genomic_DNA. DR CCDS; CCDS5530.1; -. [P08236-1] DR CCDS; CCDS64665.1; -. [P08236-3] DR PIR; A26581; A26581. DR RefSeq; NP_000172.2; NM_000181.3. [P08236-1] DR RefSeq; NP_001271219.1; NM_001284290.1. [P08236-3] DR RefSeq; NP_001280033.1; NM_001293104.1. DR RefSeq; NP_001280034.1; NM_001293105.1. DR RefSeq; XP_005250354.1; XM_005250297.3. [P08236-2] DR PDB; 1BHG; X-ray; 2.53 A; A/B=21-633. DR PDB; 3HN3; X-ray; 1.70 A; A/B/D/E=21-633. DR PDBsum; 1BHG; -. DR PDBsum; 3HN3; -. DR AlphaFoldDB; P08236; -. DR SMR; P08236; -. DR BioGRID; 109245; 96. DR DIP; DIP-29724N; -. DR IntAct; P08236; 11. DR MINT; P08236; -. DR STRING; 9606.ENSP00000302728; -. DR BindingDB; P08236; -. DR ChEMBL; CHEMBL2728; -. DR DrugBank; DB09301; Chondroitin sulfate. DR DrugBank; DB09340; Tyropanoic acid. DR CAZy; GH2; Glycoside Hydrolase Family 2. DR GlyConnect; 1037; 11 N-Linked glycans (3 sites). DR GlyCosmos; P08236; 5 sites, 12 glycans. DR GlyGen; P08236; 7 sites, 17 N-linked glycans (3 sites), 1 O-linked glycan (2 sites). DR iPTMnet; P08236; -. DR PhosphoSitePlus; P08236; -. DR SwissPalm; P08236; -. DR BioMuta; GUSB; -. DR DMDM; 146345377; -. DR EPD; P08236; -. DR jPOST; P08236; -. DR MassIVE; P08236; -. DR MaxQB; P08236; -. DR PaxDb; 9606-ENSP00000302728; -. DR PeptideAtlas; P08236; -. DR ProteomicsDB; 19519; -. DR ProteomicsDB; 52092; -. [P08236-1] DR ProteomicsDB; 52093; -. [P08236-2] DR Pumba; P08236; -. DR Antibodypedia; 14064; 435 antibodies from 36 providers. DR DNASU; 2990; -. DR Ensembl; ENST00000304895.9; ENSP00000302728.4; ENSG00000169919.17. [P08236-1] DR Ensembl; ENST00000421103.5; ENSP00000391390.1; ENSG00000169919.17. [P08236-3] DR GeneID; 2990; -. DR KEGG; hsa:2990; -. DR MANE-Select; ENST00000304895.9; ENSP00000302728.4; NM_000181.4; NP_000172.2. DR UCSC; uc003tun.4; human. [P08236-1] DR AGR; HGNC:4696; -. DR CTD; 2990; -. DR DisGeNET; 2990; -. DR GeneCards; GUSB; -. DR HGNC; HGNC:4696; GUSB. DR HPA; ENSG00000169919; Low tissue specificity. DR MalaCards; GUSB; -. DR MIM; 253220; phenotype. DR MIM; 611499; gene. DR neXtProt; NX_P08236; -. DR OpenTargets; ENSG00000169919; -. DR Orphanet; 584; Mucopolysaccharidosis type 7. DR PharmGKB; PA29075; -. DR VEuPathDB; HostDB:ENSG00000169919; -. DR eggNOG; KOG2024; Eukaryota. DR GeneTree; ENSGT00390000001752; -. DR HOGENOM; CLU_006501_6_1_1; -. DR InParanoid; P08236; -. DR OMA; IHDHVGW; -. DR OrthoDB; 1847696at2759; -. DR PhylomeDB; P08236; -. DR TreeFam; TF300685; -. DR BRENDA; 3.2.1.31; 2681. DR PathwayCommons; P08236; -. DR Reactome; R-HSA-2024096; HS-GAG degradation. DR Reactome; R-HSA-2160916; Hyaluronan uptake and degradation. DR Reactome; R-HSA-2206292; MPS VII - Sly syndrome. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; P08236; -. DR BioGRID-ORCS; 2990; 14 hits in 1165 CRISPR screens. DR ChiTaRS; GUSB; human. DR EvolutionaryTrace; P08236; -. DR GeneWiki; GUSB; -. DR GenomeRNAi; 2990; -. DR Pharos; P08236; Tchem. DR PRO; PR:P08236; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P08236; Protein. DR Bgee; ENSG00000169919; Expressed in endometrium epithelium and 208 other cell types or tissues. DR ExpressionAtlas; P08236; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0004566; F:beta-glucuronidase activity; IBA:GO_Central. DR GO; GO:0030246; F:carbohydrate binding; IBA:GO_Central. DR GO; GO:0019904; F:protein domain specific binding; IPI:AgBase. DR GO; GO:0005102; F:signaling receptor binding; IPI:AgBase. DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc. DR GO; GO:0030207; P:chondroitin sulfate catabolic process; IEA:Ensembl. DR GO; GO:0019391; P:glucuronoside catabolic process; IBA:GO_Central. DR GO; GO:0006027; P:glycosaminoglycan catabolic process; TAS:ProtInc. DR GO; GO:0030200; P:heparan sulfate proteoglycan catabolic process; IEA:Ensembl. DR GO; GO:0030214; P:hyaluronan catabolic process; IEA:Ensembl. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR InterPro; IPR036156; Beta-gal/glucu_dom_sf. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR006101; Glyco_hydro_2. DR InterPro; IPR023232; Glyco_hydro_2_AS. DR InterPro; IPR006103; Glyco_hydro_2_cat. DR InterPro; IPR023230; Glyco_hydro_2_CS. DR InterPro; IPR006102; Glyco_hydro_2_Ig-like. DR InterPro; IPR006104; Glyco_hydro_2_N. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR InterPro; IPR013783; Ig-like_fold. DR PANTHER; PTHR10066; BETA-GLUCURONIDASE; 1. DR PANTHER; PTHR10066:SF67; BETA-GLUCURONIDASE; 1. DR Pfam; PF00703; Glyco_hydro_2; 1. DR Pfam; PF02836; Glyco_hydro_2_C; 1. DR Pfam; PF02837; Glyco_hydro_2_N; 1. DR PRINTS; PR00132; GLHYDRLASE2. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF49303; beta-Galactosidase/glucuronidase domain; 1. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. DR PROSITE; PS00719; GLYCOSYL_HYDROL_F2_1; 1. DR PROSITE; PS00608; GLYCOSYL_HYDROL_F2_2; 1. DR Genevisible; P08236; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Glycoprotein; Glycosidase; Hydrolase; Lysosome; KW Mucopolysaccharidosis; Reference proteome; Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:1311180" FT CHAIN 23..651 FT /note="Beta-glucuronidase" FT /id="PRO_0000012161" FT ACT_SITE 451 FT /note="Proton donor" FT CARBOHYD 173 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218" FT CARBOHYD 420 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 631 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT VAR_SEQ 159..304 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054830" FT VAR_SEQ 305..355 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001799" FT VARIANT 30 FT /note="P -> S (in MPS7; dbSNP:rs747792546)" FT /id="VAR_058511" FT VARIANT 38 FT /note="C -> G (in MPS7; very mild phenotype; FT dbSNP:rs779499448)" FT /evidence="ECO:0000269|PubMed:9490302" FT /id="VAR_037914" FT VARIANT 52 FT /note="S -> F (in MPS7; loss of activity; FT dbSNP:rs1424546265)" FT /evidence="ECO:0000269|PubMed:9099834" FT /id="VAR_037915" FT VARIANT 136 FT /note="G -> R (in MPS7; dbSNP:rs1417426295)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037916" FT VARIANT 148 FT /note="P -> S (in MPS7; dbSNP:rs121918177)" FT /evidence="ECO:0000269|PubMed:7633414" FT /id="VAR_037917" FT VARIANT 150 FT /note="E -> K (in MPS7)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037918" FT VARIANT 152 FT /note="D -> G (in MPS7)" FT /id="VAR_058512" FT VARIANT 152 FT /note="D -> N (found in beta-glucuronidase pseudodeficiency FT with no clinical consequences; likely benign; reduced FT activity levels; dbSNP:rs149606212)" FT /evidence="ECO:0000269|PubMed:7573038, FT ECO:0000269|PubMed:9490302" FT /id="VAR_037919" FT VARIANT 176 FT /note="L -> F (in MPS7; dbSNP:rs121918181)" FT /evidence="ECO:0000269|PubMed:12859417, FT ECO:0000269|PubMed:7573038, ECO:0000269|PubMed:8089138, FT ECO:0000269|PubMed:8644704" FT /id="VAR_037920" FT VARIANT 216 FT /note="R -> W (in MPS7; dbSNP:rs121918174)" FT /evidence="ECO:0000269|PubMed:8111412, FT ECO:0000269|PubMed:8644704" FT /id="VAR_003196" FT VARIANT 243 FT /note="L -> P (in MPS7)" FT /id="VAR_058513" FT VARIANT 320 FT /note="Y -> C (in MPS7)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037921" FT VARIANT 320 FT /note="Y -> S (in MPS7; dbSNP:rs886044680)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037922" FT VARIANT 339 FT /note="N -> S (in MPS7)" FT /id="VAR_058514" FT VARIANT 350 FT /note="K -> N (in MPS7; dbSNP:rs121918182)" FT /evidence="ECO:0000269|PubMed:12522561" FT /id="VAR_037923" FT VARIANT 351 FT /note="H -> Y (in MPS7; dbSNP:rs191153460)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037924" FT VARIANT 354 FT /note="A -> V (in MPS7; dbSNP:rs121918175)" FT /evidence="ECO:0000269|PubMed:8111413" FT /id="VAR_003197" FT VARIANT 361..369 FT /note="Missing (in MPS7)" FT /id="VAR_058515" FT VARIANT 362 FT /note="D -> N (in MPS7; dbSNP:rs398123234)" FT /id="VAR_058516" FT VARIANT 364 FT /note="P -> L (in MPS7; dbSNP:rs771629102)" FT /id="VAR_058517" FT VARIANT 374 FT /note="R -> C (in MPS7; dbSNP:rs747572640)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037925" FT VARIANT 376 FT /note="L -> F (in dbSNP:rs11559283)" FT /id="VAR_055884" FT VARIANT 382 FT /note="R -> C (in MPS7; dbSNP:rs121918173)" FT /evidence="ECO:0000269|PubMed:1702266, FT ECO:0000269|PubMed:8644704" FT /id="VAR_003198" FT VARIANT 382 FT /note="R -> H (in MPS7; dbSNP:rs764018631)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037926" FT VARIANT 408 FT /note="P -> S (in MPS7; dbSNP:rs779091113)" FT /evidence="ECO:0000269|PubMed:8707294" FT /id="VAR_037927" FT VARIANT 415 FT /note="P -> L (in MPS7; dbSNP:rs751025746)" FT /evidence="ECO:0000269|PubMed:8707294" FT /id="VAR_037928" FT VARIANT 435 FT /note="R -> P (in MPS7)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037929" FT VARIANT 477 FT /note="R -> W (in MPS7; dbSNP:rs774393243)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037930" FT VARIANT 495 FT /note="Y -> C (in MPS7; dbSNP:rs121918178)" FT /evidence="ECO:0000269|PubMed:7633414" FT /id="VAR_037931" FT VARIANT 508 FT /note="Y -> C (in MPS7)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037932" FT VARIANT 540 FT /note="E -> K (in MPS7)" FT /id="VAR_058518" FT VARIANT 572 FT /note="G -> D (in MPS7)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037933" FT VARIANT 577 FT /note="R -> L (in MPS7; loss of activity; FT dbSNP:rs121918183)" FT /evidence="ECO:0000269|PubMed:12522561" FT /id="VAR_037934" FT VARIANT 606 FT /note="K -> N (in MPS7)" FT /evidence="ECO:0000269|PubMed:8644704" FT /id="VAR_037935" FT VARIANT 607 FT /note="G -> A (in MPS7; dbSNP:rs1250112198)" FT /id="VAR_058519" FT VARIANT 611 FT /note="R -> W (in MPS7; dbSNP:rs121918176)" FT /evidence="ECO:0000269|PubMed:8111413" FT /id="VAR_003199" FT VARIANT 619 FT /note="A -> V (in MPS7; dbSNP:rs121918172)" FT /evidence="ECO:0000269|PubMed:1702266" FT /id="VAR_003200" FT VARIANT 626 FT /note="Y -> H (in MPS7; very mild phenotype; FT dbSNP:rs777613366)" FT /evidence="ECO:0000269|PubMed:9490302" FT /id="VAR_037936" FT VARIANT 627 FT /note="W -> C (in MPS7; dbSNP:rs121918184)" FT /evidence="ECO:0000269|PubMed:7680524, FT ECO:0000269|PubMed:8644704" FT /id="VAR_003201" FT VARIANT 649 FT /note="L -> P (in dbSNP:rs9530)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:3468507, ECO:0000269|PubMed:8089138" FT /id="VAR_016179" FT STRAND 33..35 FT /evidence="ECO:0007829|PDB:1BHG" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 43..49 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:1BHG" FT HELIX 57..60 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 68..71 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 75..81 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 90..93 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 97..105 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 109..113 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 117..124 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 128..134 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 137..147 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 149..152 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 154..157 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 166..173 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 185..188 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 192..194 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 218..238 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 241..252 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 256..263 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:1BHG" FT STRAND 269..282 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 291..293 FT /evidence="ECO:0007829|PDB:1BHG" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 301..311 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 314..324 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 329..331 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 341..343 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 345..349 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 355..357 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 363..376 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 390..399 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 402..406 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 415..417 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 420..437 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 443..451 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 457..473 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 479..483 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 487..489 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 493..495 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 497..502 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 505..507 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 508..510 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 514..516 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 517..532 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 536..540 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 559..574 FT /evidence="ECO:0007829|PDB:3HN3" FT TURN 575..580 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 581..587 FT /evidence="ECO:0007829|PDB:3HN3" FT STRAND 600..604 FT /evidence="ECO:0007829|PDB:3HN3" FT HELIX 617..631 FT /evidence="ECO:0007829|PDB:3HN3" SQ SEQUENCE 651 AA; 74732 MW; 6BA7B1D935C9ABBD CRC64; MARGSAVAWA ALGPLLWGCA LGLQGGMLYP QESPSRECKE LDGLWSFRAD FSDNRRRGFE EQWYRRPLWE SGPTVDMPVP SSFNDISQDW RLRHFVGWVW YEREVILPER WTQDLRTRVV LRIGSAHSYA IVWVNGVDTL EHEGGYLPFE ADISNLVQVG PLPSRLRITI AINNTLTPTT LPPGTIQYLT DTSKYPKGYF VQNTYFDFFN YAGLQRSVLL YTTPTTYIDD ITVTTSVEQD SGLVNYQISV KGSNLFKLEV RLLDAENKVV ANGTGTQGQL KVPGVSLWWP YLMHERPAYL YSLEVQLTAQ TSLGPVSDFY TLPVGIRTVA VTKSQFLING KPFYFHGVNK HEDADIRGKG FDWPLLVKDF NLLRWLGANA FRTSHYPYAE EVMQMCDRYG IVVIDECPGV GLALPQFFNN VSLHHHMQVM EEVVRRDKNH PAVVMWSVAN EPASHLESAG YYLKMVIAHT KSLDPSRPVT FVSNSNYAAD KGAPYVDVIC LNSYYSWYHD YGHLELIQLQ LATQFENWYK KYQKPIIQSE YGAETIAGFH QDPPLMFTEE YQKSLLEQYH LGLDQKRRKY VVGELIWNFA DFMTEQSPTR VLGNKKGIFT RQRQPKSAAF LLRERYWKIA NETRYPHSVA KSQCLENSLF T //